Frequency of regulatory T cells in renal cell carcinoma patients and investigation of correlation with survival

Abstract

Background: Regulatory T cells are important in maintaining immune homeostasis, mediating peripheral tolerance and preventing autoimmunity. Increased frequencies of CD4+CD25high T regulatory (T Reg) cells have been documented in the peripheral blood of patients with several types of cancer consistent with a role in tumour escape from immunological control. We have investigated the presence of TReg cells systemically and in situ in previously untreated patients with renal cell carcinoma (RCC). Results: We have shown that there is a significant increased frequency of CD4+CD25high T cells in RCC patients (n = 49) compared to normal donors (n = 38), respectively, 2.47% versus 1.50%; P < 0.0001. We confirmed these data using the FOXP3 marker of TReg cells in a subset of these patients and normal donors. The population of T Reg cells identified showed the expected phenotype with CD4 +CD25high population in both RCC patients and normal donors contained higher proportions of CD45RO and GITR than CD4 +CD25-/low populations and exhibiting suppressive activity in an anti-CD3 and anti-CD28 induced proliferation assay. CD4 +FOXP3+ T cells were detected in the tumour microenvironment by immunofluorescence and the numbers enumerated in lymphocytes recovered following enzymatic disaggregations of biopsies; their frequency was higher in the tumour than the peripheral blood of the same patients. The early follow up data show an association between higher peripheral blood regulatory T-cell count and adverse overall survival. Conclusion: These data confirm the increase of TReg cells in RCC patients and provide impetus to further investigate modulation of TReg activity in RCC patients as part of therapy. © 2007 Springer-Verlag.